Oral delivery remains the preferred route for drug administration. However, therapeutic macromolecular drugs currently under development suffer from poor oral bioavailability. Nanotechnology may offer potential advantages over conventional drug delivery stratagems. In this proposal, we investigate nanofabrication approaches to create nanowire interfaces which promote bioadhesion under dynamic conditions. We examine nanostructure interactions with the underlying epithelium and the use of such interfaces to enhance the local delivery of drugs. The long-term objective of this proposal is to develop a new platform for oral delivery of pharmacologically active macromolecules into the systemic circulation via the creation of a robust bioadhesive delivery system. We propose the following specific aims: Specific Aim 1: Refine processes for optimal fabrication of highly uniform nanowire platforms of controllable size, feature geometry, mechanical integrity and uniformity Specific Aim 2: Examine mechanism of cell-nanowire bioadhesion and effects on drug release in vitro Specific Aim 3: Determine the in vivo bioadhesion of nanostructure particles using fluorescent imaging and microCT We expect to find that our nanowire-particles display enhanced bioadhesion compared to chemically modified particles. This may allow for an increase in particle residence time at the epithelial interface. In addition, the use of nanoarchitecture to enhance particle stability may mitigate issues associated with the stability of chemical modification in the GI system. PUBLIC HEALTH RELEVANCE: Oral delivery remains the preferred route for drug administration, particularly in the U.S. However, there are several issues related to adequate drug bioavailability and localization with the GI tract. We propose the use of nanostructure interfaces to enhance the bioadhesion of delivery devices to the GI tract.